奈替米星的临床研究

目的研究来替米星每日1次投药法治疗下呼吸道感染的临床效果、药代动力学、抗生素后效应和药物毒性。方法48例患者分为三组：（1）单一组14例，使用奈替米星，每天总量为6mg·kg-1·h-1；（2）合用组16例，使用头孢唑啉每12小时1次投药3g，奈替米星每天200mg；（3）对照组18例，使用头胞唑啉每12小时投药3g，与阿米卡星每天200mg联合使用，分别观察临床症状、实验室检查及临床疗效；应用荧光偏振分析仪（TDX）药物浓度自动分析仪研究其药代动力学；应用AVANTAGE生物分析仪研究奈替米星抗生素后效应，观察了奈替米星的肾、耳毒性。结果每日1次单用奈替米星组疗效较头抱叹批及阿米卡星组好。平均血药浓度为27．23mg／L谷浓度为0．23mg／L,半数药物消除相时间为5．095小时，药时曲线下面积为70μg·h-1·ml-1。奈替米皇0．5、1及4倍最低抑菌浓度（MIC）对4种细菌均显示不同程度的抗生素后效应。本组研究未发现耳、肾毒性。结论奈替米星每日1次投药法有较高血清浓度，较大药时曲线下面积，作为浓度依赖性杀菌药，此药临床效果较好，而且其抗生素后效应时间较长。

A series of clinical study on netilmicin

OBJECTIVE: To evaluate the clinical effects, pharmacokinetics, post-antibiotic effect (PAE) and toxicity of netilmicin as a single daily dose in the treatment of lower respiratory tract infection. METHODS: 48 cases were divided into 3 groups: In the first group, Netilmicin(6 mg.kg-1.d-1) was administered in a single daily dose; in the second group, netilmicin (200 mg/d) was combined with cefazolin (3 g, Q12 h); and in the third control group, the combination of cefazolin and Amikacin was used. Pharmacokinetics were studied in 7 patients using the TDX system, and PAE induced by Netilmicin was determined by the Avantage microbiologic system. Clinical symptoms, laboratory studies, chest X-rays, and side effects were observed. RESULTS: The overall clinical effects of the first group were better than those of the third group. The mean serum concentration of netilmicin was 27.23 mg/L, the valley serum concentration was 0.23 mg/L, T1/2 beta was 5.059 h, AUC was 70 micrograms.h-1.ml-1.netilmicin at concentrations 0.5, 1.0 and 4 times the MIC showed different degrees of PAE against 4 strains of bacterium. Nephrotoxicity and ototoxicity were not found in the treatment group. CONCLUSIONS: Netilmicin in a single daily dose resulted in a high peak serum concentration and big AUC. As a concentration-dependent bactericidal agent, netilmicin showed a longer PAE and better therapeutic effects.